This invention relates to novel antiviral compounds and compositions for the treatment of human viral infections. The compounds contain various combinations of nucleoside moities and various combinations of purine moities and other heterocyclic structures shown to possess antiviral activity.
The mechanism of the interference with viral reproduction in the host is varied and may be any of the following: block virus attachment to cells, block uncoating of the virus, inhibit vivid protein synthesis, inhibit specific virus enzyme, inhibit virus assembly, inhibit virus release, or simply stimulate the host immune system. There are several organic structural classes of antiviral at present: such as aminoamatadines which apparently block attachment of the virus to the cell wall of the host; a wide variety of nucleoside structures, which is a combination of a DNA or RNA base, together with a six-carbon sugar, which unlinks DNA polymerase; pyrimidines with various attached moities which also inhibit DNA polymerase.
All of these antiviral compounds have several limitations. In general the range of viruses killed or inhibited is quite narrow, commonly a single type such as influenza type A. Also, surprisingly, resistance tends to arise rapidly in the virus, requiring an endless quest for new antivirals. Alternately, as in HIV therapy, complex combinations of agents are utilized consisting of giving three or more specific drugs in a complex regime of dosage requiring constant monitoring to be sure of effectiveness. This is difficult for the patient to comply with, what with the complex pattern of when and what medication to ingest, and it is even a puzzle to physicians at times. Also, resistance develops to the medications in many patients due to the ease of genetic change by the HIV entity.
It has now been found that an alternative to the above problems of the need for a broad-spectrum antiviral drug and a drug resistant to viral genetics can be realized via chemical combinations of known effective antiviral compounds. A single example is to link two or more anti-HIV drugs by means of reaction with a linking agents such as a diacid chloride, or the like. This can be extended to the many examples developed below. The synergistic effects can be remarkable when the virus is contacted simultaneously with attacks from several quarters at the key stages of its complex life cycle in the human host cell.